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ACUTE POISONING by ATROPINE Symptoms

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NERVOUS SYSTEM PERIPHERAL CENTRAL EFFERENT AFFERENT VEGETATIVE SOMATIC SYMPATHETIC PARASYMPATHETIC SCHEME ON NEURONAL TRANSMISSION Parasympathetic n.s. Ach Ach Smooth muscles, N М heart, glands S Ach Smooth muscles, y N NA heart, glands m Ach Ach Sweat glands p N М a t Ach Renal h N D vessels e Adrenal medulla t Ach A, NА N i Ach Skeletal c muscles Somatic n. s. N SITES OF N-CHOLINORECEPTORS Central nervous system Vegetative ganglia Adrenal medulla Sinocarotid zone Skeletal muscles CHOLINERGIC SYNAPSIS presynaptic membrane Na+ Cholin Ca2+ AcCoA + Cholin Acetylcholine presynaptic receptors Cholin AchE Cholinoreceptors of postsynaptic Acetate membrane CLASSIFICATION OF CHOLINOMIMETICS М-, N- М- N- direct indirect action (anticholinesterases) reversible: Neostigmine Nico- Acetyl- Physostigmine Pilocarpine rette choline Galantamine Aceclidine Carbo- Pyridostigmine Cytiton choline irreversible: PОС, insecticides ACTIONS OF М-CHOLINOMIMETICS heart «–» ino, «–» chrono, «–» dromotropic blood dilation vessels bronchi spasm GIT peristaltics – increasing, sphincters – relaxation, secretion - increasing urinary detrusor – increasing, bladder sphincters – relaxation ACTIONS OF М-CHOLINOMIMETICS glands (sweat, lachrymal, salivary, bronchial) increasing secretion; miosis, spasm of accommodation, eye increasing of intraoccular pressure CNS hyperkinesis USES OF М-CHOLINOMIMETICS indications: Glaucoma (pilocarpine) Atony, paralytic obstruction of intestine (aceclidine) Atony of urinary bladder (aceclidine) contra-indications: Bronchial asthma Peptic ulcer of stomach Mechanic obstruction of intestine Bradyarrhythmia Epilepsy ANTICHOLINESTERASES Neostigmine, physostigmine, galantamine, pyridostigmine ACTIONS М-cholinomimetic effects + Neuro-muscular transmission – increasing INDICATIONS Glaucoma (physostigmine) Atony of urinary bladder, atony and paralytic obstruction of intestine (neostigmine) Myasthenia, paralysis, paresis, polyomyelitis, after-trauma recovery period (galantamine, neostigmine) Decurarization (galantamine, neostigmine) ACUTE POISONING BY MUSCARINE Symptoms: . CNS excitation (hallucination) . bradycardia, аtrio-ventricular blockage . bronchospasm . vomiting, diarrhea . sweating, hypersalivation . miosis, spasm of accommodation, lacrimation First aid: I.V. administration of antidote – АTROPINE (10- 15 mg !) ACUTE POISONIG BY POC Symptoms: . See muscarine poisoning + . Tonic-clonis convulsions First aid: cholinesterase re-activators – аloxim, dipyroxim, isonitrosin administration of atropine М-CHOLINOBLOCKERS Classifica Centrally Agents of Peripherally tion acting agents mixed action acting agents Agents Amizyle, Atropine, Methacine, cyclodole scopolamine, pirenzepine, beladonna iptatropium bromide extract LOCALIZATION OF CHOLINOBLOCKERS ACTION Direct action – reversible Na+ blockers of the receptors Ca2+ АcCоА + Choline М-, Н- (central) (cyclodol (trihexyphenidyl)) Acetylcholine М- (atropine, belladonna preparations , scopolamine etc М1- АCh (pirenzepine) Н- (ganglionic blockers, myorelaxants) М- or N-cholinoreceptors PHARMACODYNAMICS OF М-CHOLINOBLOCKERS together with depression of parasympathetic tonus, raising of sympathetic tonus CNS (tertiary amines) In therapeutic doses – sedative, in toxic – excitation, hallucination, aggitation, convulsions; tremor, vestibular disturbances heart (in moderate doses) «+» chronotropic (especially in young people), improvement of AV-conductivity; oxygen demand of myocardium blood vessels in toxic doses– vasodilation PHARMACODYNAMICS OF М-CHOLINOBLOCKERS GIT peristaltic – decreasing, sphincters – contraction, secretion – decreasing urinary bladder detrusor – relaxation, sphincters – contraction bronchi dilation, decreasing of secretion PHARMACODYNAMICS OF М-CHOLINOBLOCKERS mydriasis, paralysis of accommodation (cycloplegia, far sightness), eye intraocular pressure, photophobia, secretion atropine (upto 12 days) > scopolamine (3-5 days) > homatropine (15-20 hrs) > platyphyllin (5-6 hrs, without cycloplegia) > tropicamid (2-6 hs) glands (sweat, lachrymal, salivary, gastrointestinal, bronchial) secretion, body temperature (small children !) Also possess weak local anesthetic and analgesic actions USES OF М-CHOLINOBLOCKERS Preanesthetic medication (atropine) Vagus hyperactivity at heart Bronchial asthma, chronic obstructive pulmonary disease (ipratropium, tioptropim) In opthalmology with diagnostic (platyphyllin, homatropine) and treatment purpose (atropine) Peptic ulcer of stomach, hyperacidic gastritis (pirenzepine) Spasm of smooth muscles (platyphyllin, metacin) Diarrhea (belladonna agents, atropine) Motion sickness (agents, containing scopolamine) Parkinson disease (central М-cholinoblockers - cyclodol) Poisoning by muscarine, anticholinesterases (atropine) М-CHOLINOBLOCKERS Reduce tonus of smooth muscles of internal organs and inhibit secretion of exocrine glands; cause mydriasis and cycloplegia; increase Actions intraocular pressure, cause tachycardia and central cholinolytic action Bronchial asthma, spasm of smooth muscles, Therap stomach and duodenum ulcer, premedication, eutic cardiac arrest, diagnostic and treatment of ocular uses diseases, motion sickness, Parkinson’s disease, vomiting, nausea Adverse Dryness of mouth, tachycardia, constipation, effects attack of glaucoma ACUTE POISONING BY ATROPINE Symptoms: . adults – 100 mg, children – 10 mg (2-3 belladonna berries) . CNS excitation (hallucination, delirium, henbane agitation), followed by depression . tachycardia belladonna . mydriasis . dry, warm and red skin and mucosa . hyperthermia (especially children < 2 years). Dose of atropine 2 mg can be lethal ! First aid: symptomatic Intravenous physostigmine datura (1-4 mg for adults, 0,5-1 mg for children!) GANGLIONIC BLOCKERS short acting (15-20 min) – hygronium, arphonad intermediate acting (1-6 hrs) – benzohexonium, pentamine, pachycarpin long acting (6-12 hrs) – pirilen PHARMACOKINETICS Absorption: quaternary amines (benzohexonium, pentamine, hygronium) badly absorbed in GIT I.V., I.M. administration; tertiary amines (pirilen, pachycarpin) well + oral way Distribution: tertiary well cross BBB central effects (psychical disturbances, tremor etc); quaternary amines don’t cross BBB Excretion: mainly, through kidneys GANGLIONIC BLOCKERS PHARMACODYNAMICS block of N-cholinoreceptors of vegetative ganglia, so-called ”pharmacological denervation” blood sharp hypotension, especially up-right vessels: (orthostatic collapse !) because of : depression of venous tonic innervations dilation of veins decreasing of cardiac preload depression of arterial innervations dilation of arteries BP Depression of central cardiac stimulation cardiac output unloading of left ventriculus GANGLIONIC BLOCKERS PHARMACODYNAMICS heart: contractility, moderate tachycardia GIT: peristaltics – , sphincters – contraction, secretion of gastric and intestinal glands – urinary and reproductive: urine retention, erection uterus: stimulation of contractive activity (pachycarpin) eye: mydriasis, paralysis of accommodation (cycloplegia, far sightness), intraocular pressure CNS: tertiary – sedation, tremor, psychical disturbances Практически все эти эффекты не нашли клинического применения (одновременные неконтролируемые нарушения сердечно-сосудистой функции) и рассматриваются как отрицательные ! GANGLIONIC BLOCKERS THERAPEUTIC USES hypertonic crisis pulmonary edema moment-to-moment (artificial) hypotension during surgery delivery (pachycarpin) OVERDOSING acute hypotension tachycardia unconsciousness dry warm skin MYORELAXANTS (NEURO-MUSCULAR BLOCKERS Drugs relaxing the skeletal muscles • Peripheral (curare-type) • Central (for treatment of spasticity): tranquilizers (diazepam), baclofen, etc. Myorelaxants of peripheral action — the drugs relaxing the skeletal muscles due to depression of neuromuscular transmission at the level of postsynaptic membrane of the end plate Classification Nondepolarizing (competitive) action — tubocurarine, pipecuronium bromide (arduan), pancuronium bromide, vecuronium bromide, etc. Depolarizing action — dithyline (succinylcholine, succametonium chloride, listenone) Mixed action — dioxonium PHARMACODYNAMICS OF MYORELAXANTS Nondepolarizing: Depolarizing: activate N- compitetive blockade cholinoreceptors (like Ach), causing of N-cholinoceptors prolong depolarization of postsynaptic membrane ⇒ ↓ block of on postsynaptic membrane pseudocholinesterase of the skeletal muscles ⇒ removal of block by the anticholinesterase Phase I — depolarization drugs (↑ Ach content) (muscular twitching) dithyline Na+ acetylcholine (AC) tubocur arine Phase II — desensitization Na+ (muscle paralysis) N-cholinoceptors of the skeletal muscles PHARMACODYNAMICS OF MYORELAXANTS Skeletal muscles: nondepolarising: during first 1–5 min there is muscle weakness, followed by muscles paralysis in the following order: first - muscles of the eyes, jaws, then extremities, trunk, diaphragm (breathing arrest); recovery appear in the reverse order ♦ depolarizing: phase I (within 1 min) — temporary fasciculation (muscular twitching), especially of the chest, stomach, following by phase II — relaxation of muscles of the neck, extremities, face, throat, diaphragm MYORELAXANTS APPLICATION Relaxation of the muscles of larynx and throat during intubation for the inhalation anaesthesia and artificial lung ventilation Relocation and reposition of bone fragments in case of fractures Surgical operations on the abdominal and chest organs under anaesthesia with artificial ventilation of lungs Convulsions in case
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  • Pharmacology

    Pharmacology

    STATE ESTABLISHMENT «DNIPROPETROVSK MEDICAL ACADEMY OF HEALTH MINISTRY OF UKRAINE» V.I. MAMCHUR, V.I. OPRYSHKO, А.А. NEFEDOV, A.E. LIEVYKH, E.V.KHOMIAK PHARMACOLOGY WORKBOOK FOR PRACTICAL CLASSES FOR FOREIGN STUDENTS STOMATOLOGY DEPARTMENT DNEPROPETROVSK - 2016 2 UDC: 378.180.6:61:615(075.5) Pharmacology. Workbook for practical classes for foreign stomatology students / V.Y. Mamchur, V.I. Opryshko, A.A. Nefedov. - Dnepropetrovsk, 2016. – 186 p. Reviewed by: N.I. Voloshchuk - MD, Professor of Pharmacology "Vinnitsa N.I. Pirogov National Medical University.‖ L.V. Savchenkova – Doctor of Medicine, Professor, Head of the Department of Clinical Pharmacology, State Establishment ―Lugansk state medical university‖ E.A. Podpletnyaya – Doctor of Pharmacy, Professor, Head of the Department of General and Clinical Pharmacy, State Establishment ―Dnipropetrovsk medical academy of Health Ministry of Ukraine‖ Approved and recommended for publication by the CMC of State Establishment ―Dnipropetrovsk medical academy of Health Ministry of Ukraine‖ (protocol №3 from 25.12.2012). The educational tutorial contains materials for practical classes and final module control on Pharmacology. The tutorial was prepared to improve self-learning of Pharmacology and optimization of practical classes. It contains questions for self-study for practical classes and final module control, prescription tasks, pharmacological terms that students must know in a particular topic, medical forms of main drugs, multiple choice questions (tests) for self- control, basic and additional references. This tutorial is also a student workbook that provides the entire scope of student’s work during Pharmacology course according to the credit-modular system. The tutorial was drawn up in accordance with the working program on Pharmacology approved by CMC of SE ―Dnipropetrovsk medical academy of Health Ministry of Ukraine‖ on the basis of the standard program on Pharmacology for stomatology students of III - IV levels of accreditation in the specialties Stomatology – 7.110105, Kiev 2011.